NM_015055.4:c.1513C>A

Variant names:

• chr11-9748015-C-A
• rs415895
• NM_015055.4:c.1513C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015055.4(SWAP70):​c.1513C>A​(p.Gln505Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SWAP70 NM_015055.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.52
• Publications: 60 publications found

Genes affected

SWAP70 (HGNC:17070): (switching B cell complex subunit SWAP70) Enables cadherin binding activity. Predicted to be involved in regulation of actin polymerization or depolymerization. Predicted to act upstream of or within isotype switching. Located in actin cytoskeleton; cytoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23346299).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015055.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SWAP70	NM_015055.4	MANE Select	c.1513C>A	p.Gln505Lys	missense	Exon 10 of 12	NP_055870.2
	SWAP70	NM_001297714.2		c.1339C>A	p.Gln447Lys	missense	Exon 9 of 11	NP_001284643.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SWAP70	ENST00000318950.11	TSL:1 MANE Select	c.1513C>A	p.Gln505Lys	missense	Exon 10 of 12	ENSP00000315630.6
	SWAP70	ENST00000447399.6	TSL:2	c.1339C>A	p.Gln447Lys	missense	Exon 9 of 11	ENSP00000399056.2
	SWAP70	ENST00000534562.1	TSL:5	n.*699-2269C>A		intron	N/A	ENSP00000433824.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 63

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.18	T
Eigen	Benign	0.050
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.5
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.043
Sift	Benign	0.093	T
Sift4G	Benign	0.29	T
Polyphen		0.0020	B
Vest4		0.28
MutPred		0.24		Gain of ubiquitination at Q505 (P = 0.0066)
MVP		0.32
MPC		0.47
ClinPred		0.77	D
GERP RS		5.7
Varity_R		0.22
gMVP		0.30
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs415895; hg19: chr11-9769562;